Is C3 p.Arg668fs (c.2002del) pathogenic?

C3 p.Arg668fs (c.2002del) is classified Pathogenic in C3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-30). Associated with complement component 3 deficiency.

What condition is associated with C3 p.Arg668fs (c.2002del)?

C3 p.Arg668fs (c.2002del) is associated with complement component 3 deficiency (ClinVar).

How is Complement component 3 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

C3 p.Arg668fs

c.2002del · VCV4280162

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

complement component 3 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 16 of 41
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.6	GERP 1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: C3
Protein: p.Arg668fs
Coding: c.2002del
MANE Select: NM_000064
Type: Deletion
Location: chr19:6707511 (GRCh38)
Gene constraint: LOEUF 0.541 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.84 · 80 PDB
Residue 668: a disulfide bond

Full C3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

complement component 3 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Complement component 3 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

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C3 p.Asn1229fs Likely pathogenic ★ same condition
C3 p.Asn93fs Likely pathogenic ★ same condition
C3 p.Glu1640fs Likely pathogenic ★ same condition
C3 p.Glu299fs Likely pathogenic ★ same condition
C3 p.Phe872fs Likely pathogenic ★ same condition
C3 p.Thr1333fs Pathogenic ★ same condition
C3 p.Val57fs Pathogenic ★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/c3-p-arg668fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown